The United States Food and Drug Administration (FDA) recently inspected your firm, located in Cleveland, Ohio, on April 18 through 26, 2007 (April inspection), as a result of you recalling your hydroflurocarbon (HFC) products and as a follow-up to a March 6 through 15, 2007 inspection (March inspection), which resulted in the recall and discontinued manufacture of your artificial saliva product (Salivart). During the April inspection, an FDA investigator confirmed that your firm is now contracting out the manufacture of Salivart and have placed the manufacturing of your HFC products on hold. Under section 201(h) of the Federal Food, Drug and Cosmetic Act (the Act), 21 U.S.C. § 321(h), these products are devices because they are intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, or are intended to affect the structure or function of the body.

The April inspection revealed that these devices are adulterated within the meaning of section 501(h) of the Act, 21 U.S.C. § 351(h), in that the methods used in, or the facilities or controls used for manufacturing, packing, storage, or installation are not in conformity with the Current Good Manufacturing Practice (CGMP) requirements of the Quality System (QS) regulation found at Title 21, Code of Federal Regulations (CFR), Part 820. We received a response from Amy J. Paukovits, Director of Regulatory Affairs, dated May 10, 2007 (Response Letter), concerning our investigator's observations noted on the Form FDA 483, List of Inspectional Observations (FDA 483), that was issued to your firm. We address this response below, in relation to each of the noted violations. These violations include:

1. Failure to fully document or reference in your corrective and preventive action (CAPA) files, the failure investigations that your firm had planned to perform as a result of the microbial contamination of Salivart. [21 CFR § 820.100(b)]

Specifically, during the March inspection, the FDA investigator requested copies of all CAPAs/complaints/investigations regarding the contamination issue surrounding the Salivart product. CAPA 07-002 with an initiation date of January 15, 2007, which pertained to the microbial contamination of Salivart, did not contain documentation for all of the failure investigations that your firm had planned. As part of the Salivart contamination problem, your firm decided to test HFC products that were manufactured on the same line as the Salivart. On March 6, 2007, CAPA 07-006, which dealt with unacceptable levels of mold found in the Pain Ease medium (HFC Product), was opened. This CAPA was not provided to the FDA investigator during the March inspection when he requested all CAPAs/complaints/investigations relating to Salivart recall. Your firm also did not provide him any of the emails, memos, or root cause analysis documents pertaining to the HFC products, all of which had January and February 2007 dates. Not until the April inspection did you provide the FDA investigator with copies of these documents and inform him that you had opened CAPA 07-006.

We have reviewed your response to this observation and have concluded that it is inadequate, because neither the Response Letter, nor your newly drafted CAPA procedure (attached to the Response Letter), addresses the steps your firm will take to assure that the planned failure investigations are referenced or documented in your CAPA files.

2. Failure to develop procedures for and to inspect and test the Heating and Cooling (HVAC) system to assure there is no contamination of fungi, molds, and microorganisms. [21 CFR § 820.70(c)] Specifically, the HVAC system has been identified as the root cause of mold contamination of the HFC product.

Your response to this observation appears adequate.

The April inspection also revealed that your Salivart is misbranded under section 502(t)(2) of the Act, 21 U.S.C. § 352(t)(2), in that your firm failed or refused to furnish material or information respecting the device that is required by or under section 519 of the Act, 21 U.S.C. § 360i, and 21 CFR Part 803 Medical Device Reporting (MDR) regulation. Significant deviations include, but are not limited to, the following:

Failure to submit an MDR to FDA within 30 days of receiving information that your marketed device may have caused or contributed to a death or serious injury. [21 CFR § 803.50(a)(1)] Specifically:

Complaint 20071033, dated March 12, 2007, documents a user of Salivart, who became sick after using the product. The letter from the user's spouse states the user was admitted to the hospital with symptoms and side effects as those your company described in the recall notice for Salivart, and has been in the hospital for three weeks.

Complaint 20071036, dated March 14, 2007, documents a user of Salivart, who describes having symptoms of dehydration, nausea, vomiting, stomach cramps and weight loss. The user was admitted to the hospital for dehydration.

Your response to this observation appears adequate, and FDA has received MDRs from your firm on these two events.

You should take prompt action to correct the violations addressed in this letter. Failure to promptly correct these violations may result in the initiation of regulatory action without further notice. This may include, but is not limited to, seizure, injunction, and/or civil money penalties. Also, federal agencies are advised of the issuance of all Warning Letters about devices so that they may take this information into account when considering the award of contracts. Additionally, premarket applications for Class III devices to which the Quality System regulation deviations are reasonably related will not be approved until the violations have been corrected. Requests for Certificates to Foreign Governments will not be granted until the violations related to the subject devices have been corrected.

Please notify this office within fifteen (15) working days from the date you receive this letter of the specific steps you have taken to correct the noted violations, including an explanation of how you plan to prevent these violations, or similar violations, from occurring again. Include documentation of the corrective actions you have taken. If your planned corrective actions will occur over time, please include a timetable for implementation of those corrections. If corrective action cannot be completed within 15 working days, state the reason for the delay and the time within which the corrections will be completed.

Your response should be sent to Ms. Gina Brackett, Compliance Officer, Food and Drug Administration 6751 Steger Drive, Cincinnati, Ohio 45237. If you have any questions concerning the contents of this letter, you may contact Ms. Brackett at (513) 679-2700, ext. 167, or you may forward a facsimile to her at (513) 679-2773.

Finally, you should know that this letter is not intended to be an all-inclusive list of violations at your facility. It is your responsibility to ensure compliance with applicable laws and regulations administered by the FDA. The specific violations noted in this letter and in the FDA 483s may be symptomatic of serious problems in your firm's manufacturing and quality assurance systems. You should investigate and determine the causes of the violations, and take prompt action to correct the violations and to bring your products into compliance.